Biochemistry, Biophysics, and Structural Biology Commons^™

Transcriptome-Wide Identification Of The Rna-Binding Landscape Of The Chromatin-Associated Protein Parp1 Reveals Functions In Rna Biogenesis, Manana Melikishvili, Julia H. Chariker, Eric C. Rouchka, Yvonne N. Fondufe-Mittendorf

Molecular and Cellular Biochemistry Faculty Publications

Recent studies implicate Poly (ADP-ribose) polymerase 1 (PARP1) in alternative splicing regulation, and PARP1 may be an RNA-binding protein. However, detailed knowledge of RNA targets and the RNA-binding region for PARP1 are unknown. Here we report the first global study of PARP1–RNA interactions using PAR–CLIP in HeLa cells. We identified a largely overlapping set of 22 142 PARP1–RNA-binding peaks mapping to mRNAs, with 20 484 sites located in intronic regions. PARP1 preferentially bound RNA containing GC-rich sequences. Using a Bayesian model, we determined positional effects of PARP1 on regulated exon-skipping events: PARP1 binding upstream and downstream of the skipped exons …

Defining Electron Bifurcation In The Electron-Transferring Flavoprotein Family, Amaya M. Garcia Costas, Saroj Poudel, Anne-Frances Miller, Gerrit J. Schut, Rhesa N. Ledbetter, Kathryn R. Fixen, Lance C. Seefeldt, Michael W. W. Adams, Caroline S. Harwood, Eric S. Boyd, John W. Peters

Chemistry Faculty Publications

Electron bifurcation is the coupling of exergonic and endergonic redox reactions to simultaneously generate (or utilize) low- and high-potential electrons. It is the third recognized form of energy conservation in biology and was recently described for select electron-transferring flavoproteins (Etfs). Etfs are flavin-containing heterodimers best known for donating electrons derived from fatty acid and amino acid oxidation to an electron transfer respiratory chain via Etf-quinone oxidoreductase. Canonical examples contain a flavin adenine dinucleotide (FAD) that is involved in electron transfer, as well as a non-redox-active AMP. However, Etfs demonstrated to bifurcate electrons contain a second FAD in place of the …

The Molecular Mechanism Of N-Acetylglucosamine Side-Chain Attachment To The Lancefield Group A Carbohydrate In Streptococcus Pyogenes, Jeffrey Rush, Rebecca J. Edgar, Pan Deng, Jing Chen, Haining Zhu, Nina M. Van Sorge, Andrew J. Morris, Konstantin V. Korotkov, Natalia Korotkova

Molecular and Cellular Biochemistry Faculty Publications

In many Lactobacillales species (i.e. lactic acid bacteria), peptidoglycan is decorated by polyrhamnose polysaccharides that are critical for cell envelope integrity and cell shape and also represent key antigenic determinants. Despite the biological importance of these polysaccharides, their biosynthetic pathways have received limited attention. The important human pathogen, Streptococcus pyogenes, synthesizes a key antigenic surface polymer, the Lancefield group A carbohydrate (GAC). GAC is covalently attached to peptidoglycan and consists of a polyrhamnose polymer, with N-acetylglucosamine (GlcNAc) side chains, which is an essential virulence determinant. The molecular details of the mechanism of polyrhamnose modification with GlcNAc are …

Structural Basis For Earp-Mediated Arginine Glycosylation Of Translation Elongation Factor Ef-P, Ralph Krafczyk, Jakub Macošek, Pravin Kumar Ankush Jagtap, Daniel Gast, Swetlana Wunder, Prithiba Mitra, Amit Kumar Jha, Jürgen Rohr, Anja Hoffmann-Röder, Kirsten Jung, Janosch Hennig, Jürgen Lassak

Pharmaceutical Sciences Faculty Publications

Glycosylation is a universal strategy to posttranslationally modify proteins. The recently discovered arginine rhamnosylation activates the polyproline-specific bacterial translation elongation factor EF-P. EF-P is rhamnosylated on arginine 32 by the glycosyltransferase EarP. However, the enzymatic mechanism remains elusive. In the present study, we solved the crystal structure of EarP from Pseudomonas putida. The enzyme is composed of two opposing domains with Rossmann folds, thus constituting a B pattern-type glycosyltransferase (GT-B). While dTDP-β-L-rhamnose is located within a highly conserved pocket of the C-domain, EarP recognizes the KOW-like N-domain of EF-P. Based on our data, we propose a structural model for …

Potential Modifications To Enzyme Replacement Therapy In Anderson-Fabry Disease, Mariam Meghdari

Dissertations, Theses, and Capstone Projects

Mutations in the GLA gene that encodes the lysosomal enzyme α-galactosidase A (αGal) result in the sphingolipidoses named Fabry disease. This enzymatic defect is inherited as an X-linked recessive disorder and is associated with a progressive deposition of glycosphingolipids, including globotriaosylceramide (GB3), galabioasylceramide, and blood group B substance in the cell. In affected males, and in some females, this leads to early death due to occlusive disease of the heart, kidney, and brain. This disease is currently treated by infusions of αGal, prolonging patients’ lives but producing antibodies against the enzyme reducing the treatment efficacy. Treatment also causes numerous and …

Improving The Thermal Stability Of Cellobiohydrolase Cel7a From Hypocrea Jecorina By Directed Evolution, Frits Goedegebuur, Lydia Dankmeyer, Peter Gualfetti, Saeid Karkehabadi, Henrik Hansson, Suvamay Jana, Vicky Huynh, Bradley R. Kelemen, Paulien Kruithof, Edmund A. Larenas, Pauline J. M. Teunissen, Jerry Ståhlberg, Christina M. Payne, Colin Mitchinson, Mats Sandgren

Chemical and Materials Engineering Faculty Publications

Secreted mixtures of Hypocrea jecorina cellulases are able to efficiently degrade cellulosic biomass to fermentable sugars at large, commercially relevant scales. H. jecorina Cel7A, cellobiohydrolase I, from glycoside hydrolase family 7, is the workhorse enzyme of the process. However, the thermal stability of Cel7A limits its use to processes where temperatures are no higher than 50 °C. Enhanced thermal stability is desirable to enable the use of higher processing temperatures and to improve the economic feasibility of industrial biomass conversion. Here, we enhanced the thermal stability of Cel7A through directed evolution. Sites with increased thermal stability properties were combined, and …

Translational Fidelity, Mistranslation, And The Cellular Responses To Stress, Kyle Mohler, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Faithful translation of mRNA into the corresponding polypeptide is a complex multistep process, requiring accurate amino acid selection, transfer RNA (tRNA) charging and mRNA decoding on the ribosome. Key players in this process are aminoacyl-tRNA synthetases (aaRSs), which not only catalyse the attachment of cognate amino acids to their respective tRNAs, but also selectively hydrolyse incorrectly activated non-cognate amino acids and/or misaminoacylated tRNAs. This aaRS proofreading provides quality control checkpoints that exclude non-cognate amino acids during translation, and in so doing helps to prevent the formation of an aberrant proteome. However, despite the intrinsic need for high accuracy during translation, …

Carbonyl Reduction By Ymfi Completes The Modification Of Ef-P In Bacillus Subtilis To Prevent Accumulation Of An Inhibitory Modification State, Katherine R. Hummels, Anne Witzky, Andrei Rajkovic, Rodney Tollerson Ii, Lisa A. Jones, Michael Ibba, Daniel B. Kearns

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Translation elongation factor P (EF‐P) in Bacillus subtilis is required for a form of surface migration called swarming motility. Furthermore, B. subtilis EF‐P is post‐translationally modified with a 5‐aminopentanol group but the pathway necessary for the synthesis and ligation of the modification is unknown. Here we determine that the protein YmfI catalyzes the reduction of EF‐P‐5 aminopentanone to EF‐P‐5 aminopentanol. In the absence of YmfI, accumulation of 5‐aminopentanonated EF‐P is inhibitory to swarming motility. Suppressor mutations that enhanced swarming in the absence of YmfI were found at two positions on EF‐P, including one that changed the conserved modification site (Lys …

Fret Biosensors: Engineering Fluorescent Proteins As Biological Tools For Studying Parkinson’S Disease, Nathan J. Leroy, Jacob R. Norley, Saranya Radhakrishnan, Mathew Tantama

The Summer Undergraduate Research Fellowship (SURF) Symposium

Parkinson’s Disease (PD) is a common neurodegenerative disease with over 200,000 new cases each year. In general, the cause of the disease is unknown, but oxidative stress inside of neurons has been associated with the disease’s pathology for some time. Currently, techniques to study the onset of PD inside of neurons are limited. This makes treatments and causes difficult to discover. One solution to this has been fluorescent protein biosensors. In short, these proteins can be engineered to glow when a certain state is achieved inside a cell. The present research discusses the engineering of a genetically-encoded fluorescent protein (FP) …

Elongation Factor P Interactions With The Ribosome Are Independent Of Pausing, Rodney Tollerson Ii, Anne Witzky, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Bacterial elongation factor P (EF-P) plays a pivotal role in the translation of polyproline motifs. To stimulate peptide bond formation, EF-P must enter the ribosome via an empty E-site. Using fluorescence-based single-molecule tracking, Mohapatra et al. (S. Mohapatra, H. Choi, X. Ge, S. Sanyal, and J. C. Weisshaar, mBio 8:e00300-17, 2017, https://doi.org/10.1128/mBio.00300-17 ) monitored the cellular distribution of EF-P and quantified the frequency of association between EF-P and the ribosome under various conditions. Findings from the study showed that EF-P has a localization pattern that is strikingly similar to that of ribosomes. Intriguingly, EF-P was seen to bind ribosomes more …

Peptide Inhibitors Targeting The Neisseria Gonorrhoeae Pivotal Anaerobic Respiration Factor Ania, Aleksandra E. Sikora, Robert H. Mills, Jacob V. Weber, Adel Hamza, Bryan W. Passow, Andrew Romaine, Zachary A. Williamson, Robert W. Reed, Ryszard A. Zielke, Konstantin V. Korotkov

Molecular and Cellular Biochemistry Faculty Publications

Neisseria gonorrhoeae causes the sexually transmitted infection gonorrhea, which is highly prevalent worldwide and has a major impact on reproductive and neonatal health. The superbug status of N. gonorrhoeae necessitates the development of drugs with different mechanisms of action. Here, we focused on targeting the nitrite reductase AniA, which is a pivotal component of N. gonorrhoeae anaerobic respiration and biofilm formation. Our studies showed that gonococci expressing AniA containing the altered catalytic residues D137A and H280A failed to grow under anaerobic conditions, demonstrating that the nitrite reductase function is essential. To facilitate the pharmacological targeting of AniA, new crystal structures …

Gcn5 Impacts Fgf Signaling At Multiple Levels And Activates C-Myc Target Genes During Early Differentiation Of Embryoid Bodies, Li Wang

Dissertations and Theses (Open Access)

Precise control of gene expression during development is orchestrated by transcription factors, signaling pathways and co-regulators, with complex cross-regulatory events often occurring. Growing evidence has identified chromatin modifiers as important regulators for development as well, yet how particular chromatin modifying enzymes affect specific developmental processes remains largely unclear. Embryonic stem cells (ESCs) are self-renewing, pluripotent, and have the abilities to generate almost all cell types in adult tissues. The dual capacity of ESCs to self-renew and differentiate offers unlimited potential for studying gene regulation events at specific developmental stages in vitro that parallel developmental events during embryogenesis in vivo. …

Application Of Open-Access Databases To Determine Functional Connectivity Between Resveratrol-Binding Protein Qr2 And Colorectal Carcinoma, Barbara B. Doonan, Evelien Schaafsma, John T. Pinto, Joseph M. Wu, Tze-Chen Hsieh

NYMC Faculty Publications

Colorectal cancer (CRC) is a major cause of cancer-associated deaths worldwide. Recently, oral administration of resveratrol (trans-3,5,4'-trihydroxystilbene) has been reported to significantly reduce tumor proliferation in colorectal cancer patients, however, with little specific information on functional connections. The pathogenesis and development of colorectal cancer is a multistep process that can be categorized using three phenotypic pathways, respectively, chromosome instability (CIN), microsatellite instability (MSI), and CpG island methylator (CIMP). Targets of resveratrol, including a high-affinity binding protein, quinone reductase 2 (QR2), have been identified with little information on disease association. We hypothesize that the relationship between resveratrol and different CRC etiologies …

Syk Inhibitors In Clinical Development For Hematological Malignancies, Delong Liu, Aleksandra Mamorska-Dyga

NYMC Faculty Publications

Spleen tyrosine kinase (Syk) is a cytosolic non-receptor protein tyrosine kinase (PTK) and is mainly expressed in hematopoietic cells. Syk was recognized as a critical element in the B-cell receptor signaling pathway. Syk is also a key component in signal transduction from other immune receptors like Fc receptors and adhesion receptors. Several oral Syk inhibitors including fostamatinib (R788), entospletinib (GS-9973), cerdulatinib (PRT062070), and TAK-659 are being assessed in clinical trials. The second generation compound, entospletinib, showed promising results in clinical trials against B-cell malignancies, mainly chronic lymphoid leukemia. Syk inhibitors are being evaluated in combination regimens in multiple malignancies.

Regulation And Modulation Of Human Dna Polymerase Δ Activity And Function, Marietta Y W T Lee, Xiaoxiao Wang, Sufang Zhang, Zhongtao Zhang, Ernest Y C Lee

NYMC Faculty Publications

This review focuses on the regulation and modulation of human DNA polymerase δ (Pol δ). The emphasis is on the mechanisms that regulate the activity and properties of Pol δ in DNA repair and replication. The areas covered are the degradation of the p12 subunit of Pol δ, which converts it from a heterotetramer (Pol δ4) to a heterotrimer (Pol δ3), in response to DNA damage and also during the cell cycle. The biochemical mechanisms that lead to degradation of p12 are reviewed, as well as the properties of Pol δ4 and Pol δ3 that provide insights into their functions …

Cellular And Molecular Targets Of Menthol Actions, Murat Oz, Eslam El Nebrisi, Keun-Hang Susan Yang, Frank Christopher Howarth, Lina T. Al Kury

Mathematics, Physics, and Computer Science Faculty Articles and Research

Menthol belongs to monoterpene class of a structurally diverse group of phytochemicals found in plant-derived essential oils. Menthol is widely used in pharmaceuticals, confectionary, oral hygiene products, pesticides, cosmetics, and as a flavoring agent. In addition, menthol is known to have antioxidant, anti-inflammatory, and analgesic effects. Recently, there has been renewed awareness in comprehending the biological and pharmacological effects of menthol. TRP channels have been demonstrated to mediate the cooling actions ofmenthol. There has been new evidence demonstrating thatmenthol can significantly influence the functional characteristics of a number of different kinds of ligand and voltage-gated ion channels, indicating that at …

Chloroformate Derivatization For Tracing The Fate Of Amino Acids In Cells And Tissues By Multiple Stable Isotope Resolved Metabolomics (Msirm), Ye Yang, Teresa W. -M. Fan, Andrew N. Lane, Richard M. Higashi

Center for Environmental and Systems Biochemistry Faculty Publications

Amino acids have crucial roles in central metabolism, both anabolic and catabolic. To elucidate these roles, steady-state concentrations of amino acids alone are insufficient, as each amino acid participates in multiple pathways and functions in a complex network, which can also be compartmentalized. Stable Isotope-Resolved Metabolomics (SIRM) is an approach that uses atom-resolved tracking of metabolites through biochemical transformations in cells, tissues, or whole organisms. Using different elemental stable isotopes to label multiple metabolite precursors makes it possible to resolve simultaneously the utilization of these precursors in a single experiment. Conversely, a single precursor labeled with two (or more) different …

Quaternary Interactions And Supercoiling Modulate The Cooperative Dna Binding Of Agt, Manana Melikishvili, Michael G. Fried

Center for Structural Biology Faculty Publications

Human O⁶-alkylguanine-DNA alkyltransferase (AGT) repairs mutagenic O⁶-alkylguanine and O⁴-alkylthymine adducts in single-stranded and duplex DNAs. The search for these lesions, through a vast excess of competing, unmodified genomic DNA, is a mechanistic challenge that may limit the repair rate in vivo. Here, we examine influences of DNA secondary structure and twist on protein–protein interactions in cooperative AGT complexes formed on lesion-free DNAs that model the unmodified parts of the genome. We used a new approach to resolve nearest neighbor (nn) and long-range (lr) components from the ensemble-average cooperativity, ω_ave. We found …

B7h6: A Cancer Biomarker For The Development Of Novel Immunotherapy Approaches, Mariana Phillips

Seton Hall University Dissertations and Theses (ETDs)

Cancer-based immunotherapy has led the evolution of biologics that can stimulate immune responses towards tumor eradication. The synthesis of small to intermediate size molecules with the targeting and effector functions of mAb may represent a novel class of immunotherapeutics that may overcome the limitations of their biological counterparts.Towards this objective, B7H6 has been identified as a protein ligand localized on the cell surface of transformed tumor cells. B7H6 binds specifically to the activating receptor NKp30, constitutively expressed on all resting and active NK cells. Upon ligand:receptor binding, B7H6 triggers NK cell activation and release of chemokines and pro-inflammatory cytokines such …

Diversity Oriented Synthesis, Characterization And Anti-Cancer Activity Of Killer Peptide Nucleolipid Bioconjugates, Niki K. Rana

Seton Hall University Dissertations and Theses (ETDs)

The killer peptide sequence D-(KLAKLAK)₂ has been originally designed and developed as an antibacterial agent. Despite having excellent cytotoxicity towards bacteria, this sequence maintains low cell cytotoxity in malignant mammalian cell types such as cancer. The chemical basis for its selectivity has been attributed to its poly(cationic) amphiphilic nature, which facilitates cell permeability across the negatively charged bacterial membrane, but with limited permeability across the zwitterionic membrane of mammalian cells. The positively charged D-(KLAKLAK)₂ sequence has been found to accumulate on the surface of the mitochondria causing dissipation of the negatively charged mitochondrial membrane potential. This charge disruption …

Microarray Dataset Of Transient And Permanent Dna Methylation Changes In Hela Cells Undergoing Inorganic Arsenic-Mediated Epithelial-To-Mesenchymal Transition, Meredith Eckstein, Matthew Rea, Yvonne N. Fondufe-Mittendorf

Molecular and Cellular Biochemistry Faculty Publications

The novel dataset presented here represents the results of the changing pattern of DNA methylation profiles in HeLa cells exposed to chronic low dose (0.5 µM) sodium arsenite, resulting in epithelial-to-mesenchymal transition, as well as DNA methylation patterns in cells where inorganic arsenic has been removed. Inorganic arsenic is a known carcinogen, though not mutagenic. Several mechanisms have been proposed as to how inorganic arsenic drives carcinogenesis such as regulation of the cell׳s redox potential and/or epigenetics. In fact, there are gene specific studies and limited genome-wide studies that have implicated epigenetic factors such as DNA methylation in inorganic arsenic-mediated …

The Foxo Transcription Factor Controls Insect Growth And Development By Regulating Juvenile Hormone Degradation In The Silkworm, Bombyx Mori, Baosheng Zeng, Yuping Huang, Jun Xu, Takahiro Shiotsuki, Hua Bai, Subba Reddy Palli, Yongping Huang, Anjiang Tan

Entomology Faculty Publications

Forkhead box O (FOXO) functions as the terminal transcription factor of the insulin signaling pathway and regulates multiple physiological processes in many organisms, including lifespan in insects. However, how FOXO interacts with hormone signaling to modulate insect growth and development is largely unknown. Here, using the transgene-based CRISPR/Cas9 system, we generated and characterized mutants of the silkworm Bombyx mori FOXO (BmFOXO) to elucidate its physiological functions during development of this lepidopteran insect. The BmFOXO mutant (FOXO-M) exhibited growth delays from the first larval stage and showed precocious metamorphosis, pupating at the end of the fourth instar (trimolter) rather …

Lymphoid Hematopoiesis And The Role Of B-Cells In Transgenic Mouse Model Of Sickle Cell Disease, Christina Cotte

University Scholar Projects

Sickle cell disease (SCD) has been shown to be associated with decreased baseline immunity and thus increased susceptibility to infection. I sought to discern possible causes of this by looking into the correlations between SCD and hematopoiesis, the immune system and the neuroendocrine system, and ultimately by conducting experiments surrounding the impaired immune system of SCD. These experiments focused on the potential causes and effects of the diminution of B-1a cells in the SCD spleen. Adoptive transfers, infections with Streptococcus pneumoniae, and histologic imaging were conducted to establish if the diminution of the B-1a cells in the SCD spleen …

Melatonin And Its Metabolites Protect Human Melanocytes Against Uvb-Induced Damage: Involvement Of Nrf2-Mediated Pathways, Zorica Janjetovic, Stuart G. Jarrett, Elizabeth F. Lee, Cory Duprey, Russel J. Reiter, Andrzej T. Slominski

Toxicology and Cancer Biology Faculty Publications

Ultraviolet light (UV) is an inducer of reactive oxygen species (ROS) as well as 6-4-photoproducts and cyclobutane pyrimidine dimers (CPD) in the skin, which further cause damage to the skin cells. Irradiation of cultured human melanocytes with UVB stimulated ROS production, which was reduced in cells treated with melatonin or its metabolites: 6-hydroxymelatonin (6-OHM), N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK), N-acetylserotonin (NAS), and 5-methoxytryptamine (5-MT). Melatonin and its derivatives also stimulated the expression of NRF2 (nuclear factor erythroid 2 [NF-E2]-related factor 2) and its target enzymes and proteins that play an important role in cell protection from different damaging factors including UVB. Silencing …

Gene 33/Mig6 Regulates Apoptosis And The Dna Damage Response Through Independent Mechanisms, Cen Li, Soyoung Park, Leonard M. Eisenberg, Hong Zhao, Zbigniew Darzynkiewicz, Dazhong Xu

NYMC Faculty Posters

Gene 33 (Mig6, ERRFI1) is an inducible adaptor/scaffold protein whose expression can be induced by both stress and mitogenic signals. It contains multiple domains for protein-protein interaction and is involved in a broad spectrum of cellular functions. Gene 33 promotes apoptosis in a cell type-dependent manner. A recent study has linked Gene 33 to the DNA damage response (DDR) induced by hexavalent chromium [Cr(VI)]. Here we show that Gene 33 induces apoptosis via both c-Abl/p73 and EGFR/AKT-dependent pathways in lung epithelial and lung carcinoma cells. Ectopic expression of Gene 33 also triggers DDR in an ATM-dependent fashion and through pathways …

Role Of Inflammation In 20-Hete Regulation Of Ischemia-Induced Angiogenesis, Elizabeth Berry, Rachel John, Samantha Tang, Austin M. Guo

NYMC Faculty Posters

Objective: 20-Hydroxyeicosatetraenoic acid (20-HETE), an important bioactive lipid metabolite, has recently been identified to be a novel contributor of angiogenesis secondary to ischemia. Moreover, an inflammatory response is required for the initiation of ischemic angiogenesis, in response to ischemic tissue injury. The goal of this study is to investigate the role of inflammation in 20-HETE regulation of ischemia-induced angiogenesis.

Methods: We first established a mouse hind limb ischemia model for immunocompetent Balb/C mice and immunodeficient NOD-SCID mice by femoral artery ligation. Groups of Balb/C and NOD-SCID mice were administered a 20-HETE synthesis inhibitor, DDMS, or saline as a solvent control. …

Pulmonary Surfactant Fortified With Cath-2 As A Novel Therapy For Bacterial Pneumonia, Brandon J. Baer

Western Research Forum

Background: Bacterial pneumonia is a leading cause of death worldwide, with high mortality rates persisting even after antibiotic treatment. Current treatments for pneumonia involve administration of antibiotics, however after the bacteria are killed they release toxic substances that induce inflammation and lung dysfunction. Host defense peptides represent a potential solution to this problem through their ability to down regulate inflammation. However, effective delivery to the lung is difficult because of the complex branching structure of the airways. My study addresses this delivery problem by using exogenous surfactant, a pulmonary delivery vehicle capable of improving spreading of these peptides throughout the …

Aberrant Coordination Geometries Discovered In The Most Abundant Metalloproteins, Sen Yao, Robert M. Flight, Eric C. Rouchka, Hunter N. B. Moseley

Molecular and Cellular Biochemistry Faculty Publications

Metalloproteins bind and utilize metal ions for a variety of biological purposes. Due to the ubiquity of metalloprotein involvement throughout these processes across all domains of life, how proteins coordinate metal ions for different biochemical functions is of great relevance to understanding the implementation of these biological processes. Toward these ends, we have improved our methodology for structurally and functionally characterizing metal binding sites in metalloproteins. Our new ligand detection method is statistically much more robust, producing estimated false positive and false negative rates of ∼0.11% and ∼1.2%, respectively. Additional improvements expand both the range of metal ions and their …

Docking Studies Of Isoform-Selectivity Of Phosphatidylinositol 3-Kinase (Pi3k) Inhibitors, Kaitlin Goettsch

UNO Student Research and Creative Activity Fair

Phosphatidylinositol 3-kinases (PI3Ks) and their related pathways are reputed targets for drug-based anticancer therapies. Mutations in PI3K genes, expression, and pathways are frequent among multiple cancer types. Four isoforms of PI3Ks exist: α, β, γ, & δ and studies have identified several ligands for each isoform which are capable of serving as inhibitory therapeutic compounds. However, the biochemical efficacy of these molecules varies and the isoform selectivity is not well understood. In this study, we applied in silico docking methods and free energy calculation methods to estimate the binding of reported PI3K ligands against 5 PI3K structures: PI3Kα (PBD ID: …

Pdip46 Is Involved In Replication Timing Control, Hsiao H. Chao, Hong Zhao, Sufang Zhang

NYMC Faculty Posters

No abstract provided.